BPH

Question 1

What is benign prostatic hyperplasia

Answer 1

After the age of 40, the prostate becomes increasingly hyperplastic.

Benign Prostatic Hyperplasia (BPH) diagnosis is divided into microscopic (histological) BPH, macroscopic BPH, radiological, urodynamic and clinical BPH, patient impact of BPH and the quality of life (IPPS score QOL)
1. Microscopic BPH
It is the proliferation of epithelial and stromal elements i.e. fibromyoadenoma.
2. Macroscopic BPH
This refers to the enlargement of the gland as it is detected clinically by DRE ie. crude estimation of size or more accurately by transrectal ultrasound or MRI. There is strong correlation between prostate size and PSA. Several studies using International Prostate Symptom Score (IPSS), Peak Flow Rate (PFR) and Urodynamics have shown that there is no direct relationship between the size of the prostate gland and lower urinary tract symptoms (LUTS).
3. Radiological
There is elevation of base of bladder on urogram and also a large filling defect.
4. Urodynamics
PFR synchronous studies of voiding pressure and postvoid residual urine (PVR).

Question 2

What is clinical BPH

Answer 2

This refers to the Lower Urinary Tract Symptoms (LUTS)
- urgency, frequency, nocturia Bladder Outlet Obstruction symptoms (BOO) intermittency, poor stream of urine, incomplete bladder emptying, retention of urine recurrent urinary tract infection, haematuria and renal insufficiency attributable to BPH.
The symptom of BPH are not entirely caused by the mass of the prostate gland and the dynamic increased urethral resistance. A significant portion of LUTS is caused by age and related detrusor dysfunction. Bladder outlet obstruction may induce much change in the bladder that contributes to LUTS.
Polyuria due to diabetes, renal insufficiencies, and other unrelated medical conditions may contribute to the LUTS.

Question 3

What is the etiology of benign prostatic hyperplasia

Answer 3

It is thought that BPH is due to altered equilibrium between cell proliferation and cell death or to stem cell disease.
The aetiological factors are complex and include ageing the presence of functioning testes and normal androgen levels.
It is rare in 20-year olds and in men castrated before pubert, or with 5-alpha reductase deficiency. Others are positive familial and genetic factors, raised DHT, increase in 5-alph reductase activity, estrogen imbalance, increased epithelia cell hyperplasia, decreased cell death of epithelial and stroma cells, stromal and epithelial cells interactions, increase activity of growth factors (GF) - fibroblast GF, transforming GF, epidermal GF, keratinocyte GF, insulin like GF, endothe lial GF,-epithelial mitogens, non-androgenic testicular sub-stances, oncogenes anti-oncogenes and povision of GF bs inflammatory cell infiltrates. The cytokines produced may also cause smooth muscle contraction.
In the stem cell theory, it is postulated that abnormalities of stem cells produce amplifying cells (which are androgen independent) which in turn produce transit cells, the comma cells in prostate which are androgen-factor dependent. This leads to transient cell proliferation. The development of BPH is the result of all these factors.
Apart from its low incidence in the Japanese, the role di race and diet is not established. There is a positive correlation between lack of physical activity, obesity and LUTS and BPH

Question 4

What is the pathology of benign prostatic hyperplasia

Answer 4

Benign prostatic hyperplasia is a fribromyoadenoma and the nodules first develop in the peri-urethral transition zone
(TZ) of the prostate near the preprostatic sphincter. All BPH nodules develop either in the TZ or in the peri-urethral region, As the disease progresses, the number of small nodules increases and they can be found in any part of the TZ and peri urethral zones unrelated to the natural enlargement of the TZ.
The capsule of the prostate gland transmits the pressure of tissue expansion due to BPH to the urethra thereby increasing the urethral resistance which produces the symptoms of LUTS (prostatism). Incision of the prostate by transurethral Collins knife improves the outflow obstruction. Dogs can develop BPH but they do not have symptoms because their prostate gland has no capsule. The size of the prostate gland does not correlate with the degree of obstruction. The symptom complex depends on the absolute size of the prostate, the dynamic urethral resistance, contraction of the smooth muscle (>60%), the prostatic capsule and the anatomical pleomorphism. Histologi-cal studies show increase in cell numbers (hyperplasia) but not hypertrophy. There is proliferation of glandular tissue and fibromuscular stroma. Gross appearance of hyperplastic tissue may show lateral and/or middle lobe enlargement and/or posterior commissural hyperplasia.
The hyperplastic nodules compress the normal periphery of the gland which forms the false capsule from which the BPH can be enucleated or resected (TURP). Depending on the relative amount of epithelial and fibromuscular tissue, the gland may be large or small and/or firm to hard. Obstruction to urine flow is due to the static component from the bulk of the glandular and fibromuscular tissue and the dynamic component due to increased contraction and tension of the smooth muscle following stimulation of the a, adrenergic nerve fibres. Blockade of the a, adrenergic nerve quickly diminishes urethral resistance and significantly improves urine flow. Androgen ablation reduces the epithelial cells and slowly decreases stromal cell numbers and marginally improves urine flow.

Question 5

What are the effects of nodular hyperplasia on bladder outflow and the bladder itself

Answer 5

Population based studies have failed to demonstrate a clear relationship between the size of the prostate and development ofsymptoms. The term lower urinary tract symptoms (LUTS) is now used to replace “prostatism” in describing symptoms associated with BPH.
These are urgency, frequency, nocturia, intemittency, weak steam, straining, incomplete bladder empting, urinary retention; acute/chronic, recurrent UTI, haematuria etc.
Most of the knowledge of the effects of bladder outflow obstruction come from experimental animal studies. The initial response to obstruction to urinary flow clinically manifests as straining, intermittency, poor stream and incomplete bladder emptying. There is compensatory hypertrophy of detrusor smooth muscles due to increased detrusor collagen.
This is seen as thickening and coarsing of muscle strands as trabeculation with widening of gaps between them to form saccules. With continued changes, the saccules develop into diverticula. The increased muscle mass, adaptation to increased intravesical pressure and maintenance of urine flow are associated with changes in the intracellular and extracel-lular parts of smooth muscle cells. This leads to detrusor instability or decreased compliance or neural detrusor response which manifests clinically by the symptom complex of frequency, urgency and nocturia. These are the 3 irritative symptoms of IPSS. The early effects are insidious and it is often difficult for patients to perceive as due to obstruction.
These irritative symptoms can be due to carcinoma-in-situ of the bladder, tuberculosis, bilharziasis of the bladder, calculi, interstitial cystitis, urinary tract infection, chronic cystitis and other causes of bladder irritation.

Decreased detrusor contractility (atonic bladder) develops in this way. The prolonged increased contractility leads to stretching of the smooth muscles and decreased ability of the muscles to contract which leads to poor urinary stream, intermittency, incomplete bladder emptying or increased residual urine, and hesitancy. These form the obstructive symptoms of IPSS. Acute urinary retention may supervene.
Progress in decreased bladder contractility, which could cause high residual urine, also causes chronic retention with overflow incontinence which is associated with loss of sensation of the distended bladder resulting from relative enervation of bladder smooth muscles. Acute or chronic retention occurs in 20-50% of patients.
When the bladder becomes overdistended, recovery of contractility after the relief of obstruction may be impossible in which case chronic, intermittent, clean, self-catheterization is needed to effect bladder emptying. This is because prolonged indwelling bladder catheter leads to recurrent UTI from ascending infection, bladder calculi, catheter cystitis and metaplasia and squamous cell carcinoma of the bladder.
As a result of the kinking of the terminal ureters as they traverse the thickened bladder, hockey stick deformity of the terminal ureters occurs associated with failure of the uretero-vesical valves, vesico-ureteric reflux, bilateral hydroureters and hydronephrosis (Fig. 47-4abc). The increased intrapelvic pressure from hydronephrosis destroys the renal papillae nephrons and parenchyma leading to impaired renal function with resulting decreased fluid, solutes and electrolyte han-dling. This causes dehydration or oedema acidosis or acute/ chronic renal failure. Decreased erythropoietin production and/or blood loss cause anaemia.
Urinary Retention: Spontaneous acute urinary retension ( AUR) in 20 - 30 % is due to infection, overdistended bladder, excessive fluid intake, alcohol, sexual activity, debility, prostatic infarction, anaesthesia, anticholinergics or surgery.
Recurrent retention accounts for about 70% of cases for surgery. Post-micturition dribbling is the third category of LUTS (post-micturion symptoms)

Question 6

What are some complications of an increasing residual urine in the bladder

Answer 6

a. Diverticula: Stasis and infection cause diverticulitis, calculi formation, squamous metaplasia and carcinoma.
b. Infection: Cystitis, epididymo-orchitis, prostatitis (ret-rograde spread into ejaculatory ducts or prostate), ascending pyelonephritis, pyonephrosis, renal and perirenal abscesses, bacteraemia, septicaemia, and septic shock, account for 12% of cases for surgery.
c. Calculi: Usually struvite (magnesium ammonium phos-phate) resulting from alkalinization of urine by urea splitting organisms (proteus vulgaris/pseudomonas, pyocyanea and kleb-siella) or mixed calcium oxalate/calcium phosphate calculi.
The prevalence of bladder calculi in bladder outlet obstruction is over 2% in uncatheterized patients but much higher in catheterized patients. Bladder outlet obstruction is the commonest cause of bladder calculi in adults and should be excluded and relieved when the stone is removed.
d. Urinary incontinence: It is usually secondary to chronic retention with overflow incontinence, detrusor instability and aging and may complicate operation in 4% of patients.

Question 7

What are some other complications of benign prostatic hyperplasia

Answer 7

These are haematuria - microscopic/macroscopic - which should be investigated like all other causes of haematuria. It may be caused by varices on the trigone, infection or calculi, diverticulitis, stone in diverticulum or carcinoma of diverticu-lum. Little is known of the ultimate mortality and morbidity of BPH because of its large prevalence and lack of population based studies. However, according to WHO reports, estimates of death from BPH from 50 countries show wide variations from 1.8/100,000 in the USA with well-developed management strategies for BPH to 29.7/100,000 in the former East Ger-many; there are no available figures in the developing world.
Statistics on the bothersomeness of the symptoms on human activities such as sleep have not been properly documented.
Post obstructive Diuresis
Sudden relief of obstruction may cause hemorrhage from relief of pressure on distended veins and post obstructive divresis from decreased tubular reabsorption of fluid and/or increased solute load of urine (urea, electrolytes, glucose infusion etc.)

Question 8

What is the correlation between bladder outlet obstruction by BPH and symptoms

Answer 8

Population-based studies have failed to demonstrate a clear relationship between the size of the prostate and the development of symptoms. The term Lower Urinary Tract Symptoms (LUTS) is now used to replace “prostatism” in describing the symptoms associated with BPH. These are urgency, fre quency, nocturia, intermittency, weak stream, straining, incomplete bladder emptying, urinary retention (acute/chronic), recurrent UTI, haematuria etc. There is little correlation between prostate size as measured by the Transrectal Ultrasonography (TRUS) and IPSS and the degree of bladder outlet obstruction as measured by (PFR/QMAX) and urodynamics pressure flow studies.

Question 9

What are some clinical features of benign prostatic hyperplasia

Answer 9

Symptoms
The primary diagnostic challenge is to establish that the symptoms are due to BPH and not to the pathological processes of ageing or other conditions such as urethral stricture, prostate cancer, etc.
1. Initial recognition
The early presentation of BPH is insidious and may not be noticed by the patients. They are recognized early by a yes answer to any of these 3 questions:
i)
do you get up at night to pass urine?

is your urine flow slow?
iii) are you bothered by your bladder function?
2. Irritative symptoms
These occur early and they are: a.
Frequency.
b. Urgency.
c.
Nocturia and.
Urge incontinence.
They have great impact on the quality of life of patients and may occur in other urinary tract pathologies such as urinary tract infection (UTI), tuberculosis, carcinoma-in-situ, bladder stones, interstitial cystitis, chronic vesical schistosomiasis, carcinoma of the prostate/or bladder, chronic prostatitis, neurogenic bladder, diabetes mellitus etc.
3. Obstructive (voiding) symptoms
These are:
a. Weak (poor) stream. b.
Feeling of incomplete bladder emptying.
C.
Straining on micturition.
d. Intermittency.
Others are:
a.
Difficulty of micturition associated with difficulty with starting micturition (hesitancy)
b.
Prolonged micturition
c. Urinary retention
This may be acute/acute on chronic or chronic.
Acute/Acute-on-Chronic.
There is sudden cessation of urination associated with painful suprapubic mass. Episodes of acute retention may be precipitated by sympathomimetic or anticholinergic drugs (e.g. Probanthine, Oxybutynin), infarct of the prostate, diuresis from diuretics, alcohol etc., or postponement of urination for long periods especially during travelling.
il) Chronic urinary retention with overflow incontinence
(“Enuresis”)
Post urination dribbling may also occur due to slow painless distension of the bladder from increasing residual urine.

4. Others
   a. Haematuria - Microscopic/macroscopic. This could be due to rupture of distended veins of bladder mucosa covering the prostate or infection, caleuli etc. It should be investigated to exclude other causes such as UTI, calculi, cancers of bladder, prostate, ureters kidneys by CT urogram, cystoscopy urinaly-sis.
   b. Recurrent UTI such as cystitis, epididymo-orchitis, pyelonephritis, bacteraemia, septicaemia etc.
   c. Renal failure - This could be acute or chronic - associated with thirst, lethargy, headaches, uraemia.

Question 10

What are some differential diagnosis of symptoms of benign prostatic hyperplasia

Answer 10

Lower Urinary Tract Symptoms

2. Obstructive Symptoms/Voiding Symptoms
   These are incomplete emptying, intermittency, poor stream, straining and retention of urine. The differential diagnosis include:
   і) BPH.
   it) Urethral stricture il) Carcinoma of prostate.
   iv) Bladder cancer of bladder neck.
   v) Bladder calculi.
   vi Phimosis/Paraphimosis.
   vil) Neurogenic bladder.
   vin Meatal stenosis
   The diagnosis is confirmed by excluding these by history, fill clinical examination and complete urological work up.

Question 11

What are the guidelines for diagnosis of benign prostatic hyperplasia

Answer 11

1. Ask the 3 questions:
   Do you get up at night to pass urine? il) Do you have problems of urine flow? iii) Is your bladder bothersome?
   If the answer to any of these is yes, then the patient has significant lower urinary tract symptoms and so the IPSS score (Table 47-1) is determined. The relevant medical history include medications - diuretics, aspirin, antihypertensives - diabetes mellitus, previous STU, operations and neurological disorders etc.

Question 12

What are some physical examinations to perform on a person suspected with BPH

Answer 12

General Examination
Anaemia, edema and dehydration are looked for. The cardiovascular system for hypertension and the chest are examined. The abdomen is examined for hernia, palpable bladder, kidneys, liver, ascites, palpable masses etc. The genitalia and penis are examined for evidence of urethral discharge, urethral stricture, meatal stenosis, perineal swell-ings, indurations, fistulae, extravasation of urine, water can serotum etc. Phimosis, paraphimosis meatal stenosis and meatal warts are looked for and the urethra palpated for induration and other abnormalities. The scrotum is examined.
Focused neurological examinations is performed. Digital rectal examination (DRE) is performed after urination and post-void residual urine (PVR) estimated. DRE is preceded by inspection and estimation of sphincter tone. The prostate is felt anteriorly for tenderness and its size (normal 20g when it is just palpable). If the finger cannot define the edges, it is estimated over 50g. The surface, mobility of the overlying rectal mucosa, the presence of median sulcus, consistency of the prostate and its symmetry are assessed. For more accurate determination of the prostate size for deciding the form of surgery, either TURP or open prostatectomy or TRUS prostate size determination is used.
Physical examination is done to rule out a neurological cause of the presenting symptoms.

Question 13

What is the definition of the consistency of the prostate and its diagnosis

Answer 13

i) In BPH, the prostate feels smooth, elastic (rubbery). il) Cancer of prostate may feel normal (TI), indurated, asymmetrical, hard with a palpable nodule, nodular, woody hard with obliterated median sulcus and a fixed overlying rectal mucosa, and in advanced cases fixation to the surrounding structures and organs.
iii) Prostatic abscess feels exquisitely tender when acute, bulky and fluctuant. A chronic abscess may not be tender. iv) In prostatitis, the acute form is exquisitely tender but
the chronic form is hard and indurated.
y The differential diagnosis of a hard prostate includes cancer, calcified/fibrotic prostate, TB of the prostate, schistosomiasis of the prostate, granulomatous prostatitis etc.
vi) Fixity of the prostate to adjacent organs - the mucosa overlying the prostate and other structures - is determined. The seminal vesicles are felt only when diseased.
The key to an accurate DRE is a good and gentle technique mastered over a long period and thinking about what the finger is doing and feeling throughout the procedure. The positive predictive value of a palpable nodule being cancer is 30%. The positive predictive value of a palpable nodule for cancer rises with levels of PSA over 4ng/ml. A palpable cancer of the prostate gland may be present with normal PSA values, if due to TCC, neuroendocrine or anaplastic disease. A normal PSA and a normal DRE indicate that there is no significant cancer.
There is some evidence that DRE causes a rise in PSA values though not signficantly. It is therefore preferable to take blood for PSA before DRE.

Question 14

What are some investigations to make in a patient with benign prostatic hyperplasia

Answer 14

1. Urinalysis: (Dipstick or spun sediment examination)
   Complete examination on midstream specimen of urine (MSU) is done for pH, sugar, proteins, crystals, culture and sensitiv-ity, microscopy for RBC, WBC, casts, crystals, bacteria and malignant cells.
   Sequential bacteriological urinalysis of voided urine- Ist portion (VI), V2 (MSU), EPS (expressed prostatic secretions) and post massage V3 are performed and the specimens examined to exclude prostatitis.
2. Full Blood Count, sickling and haemoglobinopathy.
3. Serum creatinine is done in case there is renal insuffi-ciency. 13.4% of patients with symptomatic BPH have renal insufficiency.
4. BUE, blood urea and electrolytes are checked to exclude renal insufficiency and any imbalances.
5. Serum PSA (Normal 0-4ng/ml) in < 60 years. PSA, preferably fasting blood specimen is done to exclude early prostate cancer. It is elevated in prostate cancer, BPH, prostatitis, prostate infarct and prostatic injury such as prostatic biopsy etc. The rise of PSA above 4ng/ml is an indication for prostatic biopsy, preferably by transrectal ultrasound (TRUS) Trucut biopsy technique. Other abnormalities of the PSA suchas density > 0.15ng/ml or velocity > 0.75ng/ml per year are indications for prostatic biopsy.
6. Additional Diagnostic Tests: Patients with normal initial evaluation and IPSS scores under 8 and normal PSA do not need additional investigations but are managed by watchful waiting i.e. by regular IPSS, DRE, and PSA estimations.
7. Men With Serious Complications: Patients with IPSS score over 19,complications due to BPH such as refractory urinary retention (acute/chronic), recurrent UTI, recurrent gross haematuria, bladder stones, renal insufficiency or large diverticula should be investigated for treatment by medications or surgery (TURP/TUIP/Open prostatectomy). PFR and pressure flow urodynamic studies are not possible if the patient cannot micturate or wears a urethral catheter.
8. Infection, Haematuria, Stones: Presence of these requires appropriate investigations - such as MSU, abdominal ultrasonography, plain abdominal X-ray, IVU or CT scan and urethrocystoscopy before treatment of BPH.
9. Urine Flowrate, Post-void Residual Urine, Pressure Flow Urodynamics: These tests are recommended in patients with moderate to severe symptoms - IPSS 8 - 20 - where decisions have to be taken on modalities of treatment.

Question 15

What are some differential diagnosis of BPH

Answer 15

1. Urethral Stricture (US): There is usually a history of gonococcal or sexually transmitted urethritis or urethral injury. Passage of a size 20Ch silicone urethral catheter under sterile conditions will be held up at the site of the stricture in the penile or bulbous urethra. An urethrosonography or retrograde urethrocystogram shows narrowing or complete obstruc-fion at the point of the stricture. Urethral stricture can co-exist with BPH in the same patient; in such cases the urethral stricture is treated by internal urethrotomy or urethroplasty before the treatment of the BPH.
2. Carcinoma of the prostate: DRE may reveal normal or indurated, palpable nodule, asymmetry and/or a hard prostate. The PSA is usually over 4ng/ml. Diagnosis is best confirmed by TRUS-guided sextant biopsy using an automated gun. Digital-directed transrectal Trucut biopsy is an option but sampling for carcinoma by this method is not as accurate as TRUS-guided biopsy.
3. Bladder Neck Obstruction: The patient is relatively young. The prostate is of normal size and texture by DRE and TRUS assessment. PFR is less than 10ml/sec and urethroscystoscopy shows normal size prostate trabeculated bladder but tight bladder neck.
4. Carcinoma Of The Bladder Neck: There may be microscopic or macroscopic haematuria but this may be absent in 20% ofcases. The other features are urgency and frequency incarcinoma-in-situ; urinary retention and a palpable bladder mass are late presenting features. Diagnosis is by positive urine cytology, pelvic ultrasonography, urethrocystoscopy and biopsy.
   Bladder Calculus
5. Neurogenic Bladder: This may be due to multiple sclerosis, multiple systems atrophy, brain lesions, prolapsed intervertebral disc, lesions of the spinal cord, spina bifida and myelomeningocele. Lower urinary tract symptoms may be present. Other stigmata of neurological conditions will be present such as paraesthesia of the perineum, poor anal tone, paraparesis, etc. The prostate feels- normal and urethrocystoscopy reveals absent bladder neck pathology. PFR will be < 10ml/sec and urodynamics or cystometry confirms the diagnosis. Neurogenic bladder and BPH can co-exit in the same patient. Detrussor muscle sphincter dyssynergia presents like neurogenic bladder.
6. Diabetes Mellitus: It may present with lower urinary tract symptoms of urgency, frequency and nocturia. In addition, there will be polydipsia and polyuria. There is sugar in the urine, and hyperglycaemia. Symptoms disappear when the diabetes is controlled by diet, oral hypoglycaemics/insulin but diabetes mellitus can co-exist with obstructive BPH, carcinoma of the prostate, urethral stricture or neurogenic bladder.
7. Systemic Causes of lower urinary tract symptoms include ageing, psychiatric disorders such as depression, diuretics, chronic renal failure, polydipsia and excessive consumption of beverages such as tea and coffee and water.
8. Depression: Some patients with depression lie awake at night and so may urinate frequently. The IPSS and the PFR are normal. The prostate gland is normal on DRE is normal and there is no significant post-void residual urine on pelvic ultrasonography and IVU.

Question 16

What are some complications of benign prostatic hyperplasia

Answer 16

1. Retention of urine: - acute or chronic.
2. Recurrent urinary tract infection.
3. Diverticula of bladder - Diverticulitis, calculi, carci-
   поа.
4. Hydroureter and hydronephrosis.
5. Calculus in bladder or diverticula.
6. Haematuria.
7. Progressive renal failure.
8. Effects on quality of life such as sleep, recreation, erectile function etc.

Question 17

What is the management for symptomatic BPH

Answer 17

The modern strategies for the management of symptomatic
BPH involve shared care of patients between general practitioners and urologists. This is because of the increased prevalence of the disease, the availability of several effective pharmacological preparations and the realization that watchful waiting is a reasonable option in patients with mild symptoms. The goals of treatment include relieving LUTS, decreasing BOO, improving bladder emptying, ameliorating detrussor instabil-ity, reversing renal insufficiency, and preventing future epi-
sodes of haematuria, UTI and urinary retention. The modalities of management, after full clinical history, IPSS, physical examination, DRE, urea, electrolytes, creatinine, PFR, post void residual and PSA estimations, are as follows:
1. Watchful Waiting
2. Medical Therapy
a) Alpha-1A adrenergic blockers
b) Androgen suppression (including use of stilboestrol)
C) Combination therapy - alpha-1A adrenergic blockers and androgen suppression.
Aromatase inhibitors
e) Phytotherapy
f) Future strategies
3. Minimally Invasive Treatment
a) Transurethral incision of prostate b)
Transurethral electrovaporisation of prostate.
c) Laser therapy d)
High intensity focused ultrasound
e) Others include: balloon dilatation, hyperthermia
and thermotherapy, intra-urethral stents,
transurethral needle ablation.
4. Surgery a)
Transurethral incision of prostate gland (TUIP)
(minimally invasive)
b)
Transurethral resection of prostate gland (TURP)
(minimally invasive)
c)
Transvesical prostatectomy
d)
Retropubic prostatectomy

Question 18

What is watchful waiting

Answer 18

Patients are adequately assessed. Efforts should be made to rule out cancer of the prostate by DRE, PSA and TRUS-guided prostatic biopsy where indicated. This option is usually offered to patients with IPSS < 8 who are not much bothered by the symptoms due to BPH. This involves regular 3-monthly assessment of IPSS, PFR, PSA and PVR, abdominal ultrasonography and DRE. Watchful waiting can be replaced by medical therapy or surgical treatment if the condition changes and these modalities are indicated. It is contra-indicated if there is acute or chronic retention of urine, haematuria, recurrent urinary tract infection vesical calculi, large diver-ticula, dilatation of the upper urinary tract or uraemia when surgical management is recommended.

Question 19

What is the medical therapy for symptomatic BPH

Answer 19

The patients are investigated as above and carcinoma of the prostate excluded. The ideal candidates are those with IPSS scores under 19 with bothersome symptoms. It should not be offered to patients with absolute indication for surgery such as haematuria, stones, recurrent retention, uraemia or recurrent UTI. They are carefully followed up for continuation or change in therapy if complications requiring surgery set in.
a) Alpha Adrenergic Blockers: Clinical BPH is caused mainly by dynamic obstruction of bladder neck by stromal smooth muscle contraction due to alpha-adrenergic receptor stimulation and static obstruction from the bulk of the fibromyoadenoma (Fig. 47-5b). Alpha-blockers when used relax bladder neck and prostate smooth muscle thereby increas ing urine flow. Multicentric placebo controlled studies have shown that statistically significant decreases in baseline obstructive and irritative as well as total IPSS scores cur with correct doses of alpha-adrenergic blockers. The current recommended drugs are long-acting alpha- 1-adrenergic blockers
- terazosin, alfuzosin and doxazosin and the selective alpha 1A tamsulozin. The doses of terazosin are titrated from Img to: maximum of 10mg at night depending on the individual response. The clinical response is rapid and dose-dependent, Clinically significant lowering of BP occurs in hypertensives.
Side-effects are minor and reversible and include a flu-like syndrome and dizziness. Syncope attacks may occur with the first dose or higher doses in less than 0.5% of patients. Patients should take the drugs at night and lie prostate for 30 minutes afterwards. Tamsulosin is taken in the morning. The drugs are expensive but they are effective for medical therapy d symptomatic BPH.

b) Androgen Suppression: The rationale is to reduce the level of dihydrotestosterone and thereby shrink the prostar volume so as to relieve the static obstruction.
The drugs which have been used include
i) 5-Alpha reductase inhibitors.
These are finesteride (proscar) and episteride and dutasteric are offered to patients with a large prostate gland. They inhili
5-alpha reductase, an enzyme required for conversion if testosterone to its active form 5-DHT, thereby depriving tie BPH of androgens and so causing its regression. The side effects include loss of libido and erectile dysfunction. Double. blind controlled studies show that even though they redu prostate volume by 20%, the overall reduction in IPSS scores about 1 unit fall and PFR rise is 1ml/sec and patients remas obstructed after its use. Its effect also takes a long time, about months or more, to manifest. Another problem with finesteride is that it reduces PSA levels by 50%. Therefore, the PSA kevel should be checked before treatment is started and patients hith > 4ng/ml should have a biopsy of the prostate first. The ISA values of patients on it should, therefore, be multiplied by so to get the true value so that carcinoma of the prostate is not missed.
ii) Zanoterone (100 - 800mg qid)
This is a steroid competitive androgen receptor antagonist. lihas only a minimal effect on prostate volume and PFR rise ty only 0.7ml/sec with little change in IPSS and bothersome symptoms.
Its side-effects include breast pain and
rynaecomastia.
iii) Flutamide (100 - 250 mg tid)
It is an androgen receptor antagonist. It has no significant effect on IPSS score, PFR and bothersome symptoms.
The anti-androgens are under investigation and have not moved efficacious in the treatment of BPH and their side-effects include breast pains and gynaecomastia. Finesteride treatment has minimal effect on IPSS and PFR.
c. Combination Therapy
This involves the use of combination of alpha adrenergic clockers (now found to be effective therapy for BPH) and anti-androgens in therapy for BPH. Combination of finesteride and an alpha receptor blocker eg. terazosin give only slight aditional benefit to patients.

d. Aromatase Inhibitor (Atamestane)
As estrogen causes stromal hyperplasia, inhibition of ostrogen levels by an aromatase inhibitor should lead to diminution of prostate volume. But PFR studies with atamestane showed it had no effect on PFR and prostate volume.

Phytotherapy
Various plant extracts have been used empirically to treat bwer urinary tract symptoms due to BPH. Their clinical value and safety have not been scientifically demonstrated but they heve improved IPSS and PFR. The list include:
Hypoxis roopers (South African grass). There is long-term improvement in IPSS, QOL, PFR and PVR.
il) Urtica SPP (stinging nettle). iii) Sabal serrulatum (dwarf palm). iv) Serena repens B (American dwarf palm).
V) Cucurbitapepo (pumpkin seed).
vi) Pygeum Africannum (African plum) etc. Some improvement in PFR and IPSS has been reported.
f. Future Strategies For Drug Development For Symptomatic BPH
These include the development of the following:
i)
•Endothelin antagonists to prevent contractile effect of endothelin on prostatic smooth muscle which is not abolished by alpha-adrenergic blockers.
it) Nitric oxide (NO) inhibitors may relax prostate smooth muscles which is increased by NO. ili) Non-prostate factors causing lower urinary tract symptoms such as ageing, hormonal status, non-urological disorders and neurological factors need to be identified and a new generation of therapeutic strategies developed.

Question 20

What are some minimally invasive treatments for benign prostatic hyperplasia

Answer 20

The management of BPH is of timely importance to patients, their spouses and relatives. Simple prostatectomy by transurethral resection of the prostate for small prostates or open prostatectomy (transvesical/retropubic) for large prostates remains the gold standard for reducing symptom scores (SS/IPSS), improvement of PFR or QMAX and decreasing post-void residual urine (PVR). There is associated morbidity and small mortality with TURP and open prostatectomy and so medical therapy and minimally invasive technological methods are being developed to achieve results as good as TURP and open prostatectomy at less cost and less morbidity and mortality to patients.
Invasive procedures having effect on patients should achieve at least 50% or more in the reduction of symptom score (SS/ IPSS) and 50% or more improvement of PFR. Anything achieving less is approaching a placebo effect. The traditional approaches of TURP for small prostates (less than 60g) and open prostatectomy for larger prostates or those complicated by stones and diverticula etc., remain the best procedures for producing reliable long-term results for patients. Indications for minimally invasive surgery are ill-defined but include patients with moderate symptoms scores (IPSS 8 - 19), and patients with severe symptoms but handicapped or unfit for major surgery because of poor general condition due to heart failure, myocardial infarction, liver disease, pulmonary dis-ease, neurological conditions etc. Absolute contraindications to minimally invasive surgery are:
i. Recurrent episodes of haematuria. ii. Recurrent acute or chronic retention. iii. Bladder stones due to BPH.
iv. Upper tract dilatation - hydroureters and hydronephro-sis.
v. Large diverticula. vi. Renal insufficiency.
vi. Recurrent urinary tract infections.

Available Minimally Invasive Techniques are
i. High intensity focused ultrasound (HIFU). ii. Transurethral vaporization of prostate. iii. Transurethral laser therapy (TULIP). iv. Hyperthermia and thermotherapy.
v. Intra-urethral stents.
vi. Transurethral needle ablation of prostate (TUNA). vi. Transurethral balloon dilatation.

Question 21

What are some comments on the minimally invasive treatment of benign prostatic hyperplasia

Answer 21

Patients with absolute indications for surgery, (TURP or open prostatectomy) such as refractory retention, gross haematuria, bladder stones, recurrent UTI, diverticula or renal insufficiency are not suitable for minimally invasive surgery.
Minimally invasive surgery such as transurethral electrovaporization, laser therapy, thermotherapy (TUMT), and TUNA is recommended for those with moderate IPSS (8-
19) OR SEVERE IPSS(20-35). Prostatic stents are recommended only in urinary retention in high-risk patients. Balloon dilatation and hyperthermia are not recommended at present.
1) Thermotherapy (TUMT) prostatron is recommended in patients with minimal symptoms who want minimal discomfort from treatment.
in) Laser therapy is for patients with small glands on anticoagulants or with bleeding disorder.
il) Stents are recommended in elderly high risk patients with a short life span with urinary retention. iv) For preservation of antegrade ejaculation, TUMT, laser or TUNA is used.

v) Middle lobe and bladder neck conditions are best treated by transurethral vaporization of the prostate, laser or stents because TUNA, HIFU, and TUMT are not effective.
There are no absolute indications for minimally invasive techniques because the devices are constantly changing and they have not been used for a long period.
Minimally invasive and medical therapy for BPH are contra-indicated when complications of BPH exist. These are:
1. Retention of urine - acute or chronic.
2. Recurrent urinary tract infections.
3. Diverticula.
4. Hydroureter and hydronephrosis.
5. Calculi in bladder or diverticula.
6. Haematuria.
7. Progressive renal failure.

Question 22

What is the management for retention of urine

Answer 22

Acute Retention
Relief is urgent. The procedure should first be explained to the patient. The suprapubic, scrotal and perineal areas are staved and washed if necessary and diazepam 10mg given for sedation. A sterile trolley is set up containing an antiseptic (cetrimide, povidone iodine or chlorhexidine), sterile towels, swabs, penile clamp, syringe, catheters and a specimen bottle for urine. A nurse should be on hand.
After positioning the patient comfortably, the doctor, wearing a face mask, scrubs and puts on sterile gloves. The penis, especially the glans, is cleansed with an antiseptic and sterile towels arranged around it. About 2-5mls of lidocaine 1% jelly is instilled into the urethra and massaged into it and retained by clipping the glans with a penile clamp or by applying pressure with the thumb and finger. The urethra is anaesthetized in 4-5 minutes.
A suitable 100% silicone catheter is selected - Jacques, Foley’s, Nelaton Tiemann’s or Gibbon’s. A wide-bore 3-way or 2-way 100% silicone Foley’s catheter is used if bleeding or irrigation is anticipated and a Nelaton catheter if not for indwelling. Otherwise a narrow (12F) plastic Jacques catheter is selected. An indwelling 100% silicone catheter should not fit tightly so that the secretions of the para-urethral glands can drain alongside it. Obstruction of the para-urethral glands by a tight catheter may lead to infection and subsequent development of stricture.
The penis is held straight and the 100% silicone catheter inserted into the external meatus and gently advanced into the urethra. At the external sphincter there may be some resistance or discomfort. In that event, the doctor waits while the patient is asked to relax, thereby opening up the sphincter, and to breathe in and out. The catheter is then slowly advanced into the bladder at which event urine flows out if urine does not flow out the catheter is irrigated by 10mls sterile water saline to get urine flow. Urine is collected in a sterile bottle for culture and sensitivity, sugar and protein tests.
The urine is then drained and the catheter is retained for urgent urological consultation. Normal micturition may be resumed after treating with alpha-adrenergic blockers. If not, a self-retaining silastic Foley’s catheter is inserted. A sterile urine bag is connected to the catheter for closed bladder drainage. The urine bag is drained every 24h under aseptic conditions to prevent infection. The catheter may be connected to a closed plastic container fitted with a non-return valve.
There should be antibiotic prophylaxis.

If there is difficulty in inserting a catheter, a suprapubic needle puncture or stab suprapubic cystostomy or cystofix is made. A polythene tube with multiple side holes is then passed through the needle and the needle removed or Foley’s catheter passed through the cannula of stab suprapubic device. The tube is connected to a closed sterile plastic urine bag. If the catheter cannot be weaned off after trial of medical treatment for 3-4 weeks, then after appropriate investigations TURP or simple prostatectomy is performed, as soon as possible.

Question 23

What is chronic retention

Answer 23

Urgent blood urea, creatinine and electrolytes and ultrasound scan of the bladder and kidneys are done.
a) If the kidney function is satisfactory, prostatectomy is undertaken at the next operating session.
b) Chronic retention of urine and uraemia: If there is impairment of renal function, preliminary bladder decompression and correction of fluid and urea electrolyte imbalances, acidosis, anemia and treatment of UTI are required. Rapid decompression may lead to bleeding or post-obstructive diure-sis.
A self-retaining 100% silastic catheter is inserted under the same conditions as described under acute retention.
After 2-3 weeks, the patient may improve sufficiently for simple prostatectomy to be done. In severe cases dialysis - haemo- or peritoneal or prolonged drainage up to 3 or 4 months may be required. The 100% silastic urethral catheter is changed every 2-3 weeks. Antibiotic cover is necessary.
c) In chronic retention of urine and decompensated non-contractile bladder, the patient is initially managed by clean intermittent self-catheterization (CISC) until the bladder regains normal contractility before prostatectomy is undertaken.
Otherwise the patient is managed permanently by CISC.

Question 24

What is a bleeding BPH and clot retention

Answer 24

The patient undergoes a full clinical history and physical examination. An IV line is set up with normal saline and blood taken for full blood count, group and crossmatch. He is then sedated and a large size 3-way Foley’s catheter (22-26Ch) passed into the bladder under 100% silicone aseptic conditions.
Using a 50ml bladder syringe, all blood clots are evacuated and the bladder irrigated until the fluid from it is clear. Continuous irrigation is maintained and the patient prepared for prostatectomy by TURP or open method after abdominal ultrasonography and urethrocystoscopy. Blood transfusion is instituted in the pre-operative and peri-operative periods as required.

Question 25

What are some indications for prostatectomy

Answer 25

i) Acute refractory urinary retention.
ii) Chronic urinary retention.
iii) Recurrent episodes or severe haematuria. iv) Bladder stones secondary to BPH.
v) Recurrent attacks of urinary infections in patients with BPH.
vi) Large bladder diverticula.
vii) Upper tract dilatation due to BPH. viii) Uraemia (azotaemia) due to BPH.

The other indications are
i) Symptoms of bladder outlet obstruction due to BPH which are moderate to severe, bothersome and interfere with the patients quality of life (usually IPSS score from 19 to 35) but which are not relieved by medical therapy or minimally invasive surgery.

Question 26

What are some contraindications to a prostatectomy

Answer 26

These are not absolute but depend on the competence of the team managing the patient and the availability of supportive medical facilities. They include:
i. Frail elderly patients.

ii. Patients with severe co-morbidity such as myocardial infarct, heart disease ureamia, liver failure, pulmonary dis-ease, carcinomatosis etc.
iii. A severe bleeding tendency and patients on anticoagu-lants. Patients on regular aspirin or herbal medicine can be safely operated on after stopping aspirin or herbal medicine for a minimum of 10 days and checking bleeding and clotting times and after finasteride therapy.

Question 27

What goes into pre-operative preparation for BPH

Answer 27

100% silastic catheter drainage is mandatory before opera tion in the patient who presents with acute retention or acute. on-chronic retention; it is unnecessary in those with only obstructive symptoms. The use of prophylactic antibiotics i advised.
Before surgery, it is essential to correct dehydration uraemia and electrolyte imbalances. The patient should be screened to exclude inadequate pulmonary function, diabetes mellitus and cardiac disease. Uraemia should be corrected by 100% silicone catheter drainage until the blood urea level and serum creatinine fall to acceptable levels. Anemia is cor rected by adequate blood transfusion. Nutritional deficiencies should also be corrected.
The IPSS, urine flowrate and DRE are done urethrocystoscopy at the time of prostatectomy is recon-mended. Urethrocystoscopy before planned prostatectomy: indicated in patients with haematuria, diverticula, or recurrent UTI. Upperurinary tract imaging by ultrasonography or IV CT urogram is recommended in recurrent UTI, haematuriad urinary stones, as well as previous urinary tract surgery fort large prostate for an accurate determination of its size Routine abdomino-pelvic ultrasound is recommended butros tine IVU is not as the positive yield is less than 10% Urodynamics and pressure flow studies are recommended when the diagnosis is uncertain especially in those wit dominant irritative symptoms.

Question 28

What are some surgical options for BPH

Answer 28

These are:
1. Transurethral incision of the prostate (TUIP).
2. Transurethral resection of the prostate (TURP).
3. Open simple prostatectomy.
a) Transvesical prostatectomy.
b) Retropubic prostatectomy.
The aim of simple prostatectomy is to relieve the outflor obstruction by removal of the adenomatous hyperplasia from the inner shell of the compressed prostatic capsule.
Cystoscopy must be done before prostatectomy in order identify any concomitant lesions in the bladder, the simulti-neous management of which would determine the best approsa for the prostatectomy.